Abstract

BackgroundSurgery under cardiopulmonary bypass (CPB) is still associated with significant cardiovascular morbidity in both pediatric and adult patients but the mechanisms are not fully understood. Abnormalities in coronary flow and function have been suggested to play an important role. Prior studies suggest protective effects on coronary and myocardial function by short intravenous (i.v.) infusion of cyclosporine A before CPB.MethodsBarrier-bred piglets (10–12 kg, n=20) underwent CPB for 45 min, with or without antegrade administration of cardioplegic solution. Prior to CPB, half of the animals in each group received an i.v. infusion of 100 mg/kg cyclosporine A. The left anterior descending coronary flow velocity responses to adenosine, serotonin, and atrial pacing, as well as left ventricular function and postsurgical vulnerability to atrial fibrillation (Afib) were assessed by intracoronary Doppler, epicardial echocardiography, and in vivo electrophysiological study, before and 8 hours after surgery. Plasma C-reactive protein (CRP) and fibrinogen were measured at both time-points.ResultsCyclosporine infusion did not influence any of the studied variables (p>0.4). Coronary peak flow velocity (cPFV) rose significantly after surgery especially in the cardioplegia group (p<0.01 vs. non-cardioplegia group and pre-surgery). cPFV responses to adenosine, but not to serotonin, tended to decrease (p=0.06) after surgery only in cardioplegia group (p=0.06; p=0.8 in non-cardioplegia group vs pre-surgery). Also, cPFV response to atrial pacing was lower in the cardioplegia than in the non-cardioplegia group (p=0.02). Neither vulnerability nor duration of induced Afib after CPB differed between groups (Chi-square p=0.4). Cyclosporine had no significant effect on coronary indexes or arrhythmia vulnerability (p>0.4). There was no difference in systolic myocardial function between groups at any time point.ConclusionIn piglets, CPB with cardioplegia was associated with profound abnormalities in coronary vasomotor tone and receptor-related flow regulation, whereas arrhythmia vulnerability appeared to be comparable with that in non-cardioplegia group. In this study, preconditioning with cyclosporine had no detectable protective effect on coronary circulation or arrhythmia vulnerability after CPB.

Highlights

  • Surgery under cardiopulmonary bypass (CPB) is still associated with significant cardiovascular morbidity in both pediatric and adult patients but the mechanisms are not fully understood

  • We investigated whether administration of normothermic blood cardioplegia influence coronary and myocardial function after CPB in young miniaturized pigs, and whether these changes could be prevented by preoperative intravenous infusion of cyclosporine A

  • Cyclosporine on post-CPB variables Cyclosporine had no significant effect on coronary indexes or arrhythmia vulnerability (p>0.4)

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Summary

Introduction

Surgery under cardiopulmonary bypass (CPB) is still associated with significant cardiovascular morbidity in both pediatric and adult patients but the mechanisms are not fully understood. Surgery with CPB remains associated with appreciable cardiovascular morbidity in both pediatric and adult patients [1]. A prior study suggested that coronary vasomotor function is altered by cold crystalloid cardioplegia [4], but to a less extent by warm blood cardioplegia [5]. These changes appear to involve both the microvascular [6] and epicardial [7] coronary bed with significant coronary endothelial damage and apoptosis. A study by Oka et al [8] suggested that addition of cyclosporine A to the cardioplegic solution could alleviate cardiomyocyte’s mytochondrial dysfunction and protect the myocardium against CPB-related ischemic injury

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